SIRT1 deacetylates WEE1 and sensitizes cancer cells to WEE1 inhibition.

The cell-cycle checkpoint kinase WEE1 is emerging as a therapeutic target for cancer treatment. However, how its catalytic activity is regulated remains poorly understood, and reliable biomarkers for predicting response to WEE1 inhibitor remain to be identified. Here we identify an evolutionarily conserved segment surrounding its Lys177 residue that inhibits WEE1 activity through an intermolecular interaction with the catalytic kinase domain. Upon DNA damage, CHK1-dependent phosphorylation of WEE1 at Ser642 primes GCN5-mediated acetylation at Lys177, resulting in dissociation of the inhibitory segment from the kinase domain and subsequent activation of WEE1 and cell-cycle checkpoints. Conversely, SIRT1 associates with and deacetylates WEE1, which maintains it in an inactive state. Consequently, SIRT1 deficiency induces WEE1 hyperacetylation and activation, rendering cancer cells resistant to WEE1 inhibition. These results suggest that SIRT1 expression level and abundance of WEE1 Lys177 acetylation in tumor cells can serve as useful biomarkers for predicting WEE1 inhibitor sensitivity or resistance.

Effect of Curcumol on the Fenestrae of Liver Sinusoidal Endothelial Cells Based on NF-κB Signaling Pathway.

OBJECTIVE: To study the effect of curcumol on liver sinusoidal endothelial cells (LSECs) and to analyze the mechanism of antihepatic fibrosis. METHODS: The effects of drug intervention on cell proliferation rates were detected by MTT assay. The expression of NF-κB was detected by RT-PCR and WB. The NF-κB expression and entry into the nucleus were detected by immunofluorescence; scanning electron microscopy was used to observe the changes of LSECs fenestrae. RESULTS: MTT results showed that the interference of cell proliferation in each group was small. RT-PCR showed that the expression of NF-κB in the curcumol intervention group was significantly lower than that in the positive control group (P < 0.05). The WB detection found that, in the curcumol intervention group, the expression of pNF-κB in the NF-κB signaling pathway was significantly lower than that in the positive control group (P < 0.05). Scanning electron microscopy showed that the LSEC fenestrae were significantly improved compared with the positive control group. CONCLUSION: Curcumol may be one of the mechanisms of antihepatic fibrosis by inhibiting the activity of the NF-κB signaling pathway and increasing the fenestrae of LSECs.

[Design of SCM inoculation device].

The first step of bacilli culture is inoculation bacteria on culture medium. Designing a device to increase efficiency of inoculation is significative. The new device is controlled by SCM. The stepper motor can drive the culture medium rotating, accelerating, decelerating, overturn and suspending. The device is high practicability and efficient, let inoculation easy for operator.

[The application of AI in medical consumable classifier].

Establish normal classifier of non-charge medical consumable and database of medical consumable inuse, is the basis of uniform classification and management of non-charge medical materials used in different hospital. It's an objective and effective method to classify by AI and set up the database, and has better classification accuracy.

[An ear thermometer based on infrared thermopiles sensor].

According to the development of body temperature measurement mode, an ear thermometer with infrared thermopiles sensor is designed for body thermometry Compared with oral thermometer, the accuracy of ear thermometer is acceptable.

[A biomedical signal processing toolkit programmed by Java].

According to the biomedical signal characteristics, a new biomedical signal processing toolkit is developed. The toolkit is programmed by Java. It is used in basic digital signal processing, random signal processing and etc. All the methods in toolkit has been tested, the program is robust. The feature of the toolkit is detailed explained, easy use and good practicability.

[A design of software for management of hospital equipment maintenance process].

According to the circumstance of hospital equipment maintenance, we designed a computer program for management of hospital equipment maintenance process by Java programming language. This program can control the maintenance process, increase the efficiency; and be able to fix the equipment location.

[Association of the integrin gene polymorphisms with ischemic stroke and plasma lipid levels].

OBJECTIVE: To study the association of integrin alpha-2 (ITGA2) gene C807T, integrin beta-3 (ITGB3) gene T176C polymorphisms with ischemic stroke and the effect of the polymorphisms on plasma lipid and lipoprotein levels. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing were used to detect the integrin genotypes in 265 patients with ischemic stroke and 280 healthy controls. The plasma lipid and lipoprotein levels were measured by routine method. RESULTS: Plasma total cholesterol (TC), triacylglycerol (TG) and low density lipoprotein-cholesterol (LDL-C) in the patients with ischemic stroke were significantly higher than those in the controls (P< 0.05). The distributions of the ITGB3 gene T176C polymorphism were not different between the ischemic stroke group and control group, but the ITGA2 gene C807T polymorphism was significantly different. The relative risk suffering from ischemic stroke of the T allele carrier was 1.455 times as that of the C allele carrier (OR=1.455, 95%CI: 1.134-1.866). The level of plasma lipid in the T allele carriers was significantly higher than that in the C allele carriers (P< 0.05). CONCLUSION: The ITGA2 gene C807T polymorphism was associated with ischemic stroke, the 807 T allele may be a genetic risk factor for ischemic stroke. The ITGA2 gene C807T polymorphism may affect ischemic stroke through plasma lipid and lipoprotein levels.

Platelet-endothelial cell adhesion molecule-1 gene polymorphism and its soluble level are associated with ischemic stroke.

Inflammation, characterized by the recruitment and adhesion of circulating leukocytes by cellular adhesion molecules, plays an important role in the pathogenesis of atherosclerosis. Genetic analyses of platelet-endothelial cell adhesion molecule-1 (PECAM-1), a key adhesion molecule in the progression of atherosclerosis, have provided conflicting results regarding the role of variation within the PECAM-1 gene and risk for coronary heart disease. No studies have examined the association of this polymorphism with ischemic stroke. Therefore, we investigated that PECAM-1 gene polymorphism and its soluble level are associated with ischemic stroke in Chinese population. We analyzed single-nucleotide polymorphisms of PECAM-1 gene Leu125Val, Asn563Ser, and Gly670Arg in 265 patients with ischemic stroke and 280 age- and sex-matched controls, using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing method, while soluble PECAM-1 (sPECAM-1) levels were measured by enzyme-linked immunosorbent assay. There were significant differences in the genotype and allele frequencies of PECAM-1 gene Leu125Val polymorphism between the group of patients with ischemic stroke and the control group (p < 0.05). sPECAM-1 levels were increased in patients with ischemic stroke compared with controls (p < 0.01). Moreover, genotypes carrying the PECAM-1 125Val variant allele were associated with increased PECAM-1 levels compared to the homozygous wild-type genotype in patients with ischemic stroke. The Leu125Val polymorphism of PECAM-1 and its sPECAM-1 levels are associated with ischemic stroke in Chinese population. Our data suggest that the PECAM-1 gene may play a role in the development of ischemic stroke.

[Effect of cedemex on cAMP and cGMP levels of different brain areas in morphine withdrawal rats].

OBJECTIVE: To investigate the effect of Cedemex on cAMP and cGMP contents in different brain regions in morphine withdrawal rats precipitated by naloxone. METHOD: A physical morphine dependent model of rats was established by subcutaneous injection of morphine in gradually increasing dosage within 7 days. cAMP and cGMP contents of VTA, cortex and hippocampus of the rat brains were determined by radioimmunoassay. RESULT: The morphine withdrawal symptoms of rats were relieved significantly by ig Cedemex. Compared with the controls, cAMP content in the region of VTA, cortex and hippocampus of the morphine dependent rats were significantly higher (P < 0.05), while cGMP contents in those regions were significantly lower (P < 0.05). cAMP contents in the area of VTA, cortex and hippocampus of the morphine dependent rats were significantly reduced, while cGMP contents were significantly increased by ig Cedemex. CONCLUSION: Cedemex may significantly attenuate the morphine withdrawal symptoms in rats. The mechanism of this effect may be related to adjusting the contents of cAMP and cGMP in some brain regions.